Protein kinase Cθ, a selective upstream regulator of JNK/SAPK and IL-2 promoter activation in Jurkat T cells

Abstract

The predominant expression of protein kinase C (PKC) θ in T cells (J. Biol. Chem.1993. 268: 4997– 5004), its isoenzyme-specific ability to stimulate AP-1 transcriptional activity (Mol. Cell. Biol.1996. 16: 1842 –1850) and the recent discovery of its selective and antigen-dependent colocalization with the contact region between T cells and antigen-presenting cells (Nature1997. 385: 83 – 89) suggest that, among the PKC family members, PKCθ plays a specialized role in T cell activation. By investigating the downstream effectors of PKCθ we now demonstrate a direct and isoenzyme-specific contribution of PKCθ to c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) but not extracellular regulated kinase (ERK) activation. Expression of a constitutively active (CA) form of PKCθ (but not CA-PKCα, ϵ and λ / ι) resulted in strong activation of JNK/SAPK and expression of a dominant-negative form of PKCθ interfered with the endogenous activation signal for JNK/SAPK. Importantly, Ca2+ ionophore and CA-PKCθ (but not CA-PKCα, ϵ and λ / ι) caused synergistic activation of the IL-2 promoter. Together, these data establish that PKCθ is required for activation of JNK/SAPK signaling leading to IL-2 promoter transcription in T lymphocytes.